Intranasal AD4-H5-VTN as an Adenovirus Vaccine

NCT01806909 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13008113-I-0081
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Adenoviruses are viruses that typically cause symptoms of a cold or eye infection. These viruses are being tested as part of a possible new vaccine. Researchers hope that the adenovirus will help carry the vaccine into the body and cause an immune response. An immune response is the body s release of cells and substances that protect the body from infection. If an adenovirus vaccine can be developed, it might be used as part of a vaccine for malaria or other serious illnesses. Researchers want to test the adenovirus vaccine as a nasal spray in healthy volunteers. The vaccine is called AD4-H5-VTN.
• Because the vaccine contains a live adenovirus, there is a possibility that participants can infect other people. Therefore, participants' intimate contacts must join this study. An intimate contact is someone who the participant will kiss on the mouth or have sexual intercourse with during the period of this study. Objectives:
• To study the immune response of the AD4-H5-VTN vaccine in healthy volunteers.
• To see if the adenovirus in the AD4-H5-VTN vaccine is contagious or spreads to others. Eligibility:
• Healthy volunteers between 18 and 49 years of age.
• Intimate contacts of healthy volunteers between 18 and 65 years of age.
• Participants must not have evidence of previous exposure to adenovirus type 4. Design:
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
• Participants who will receive the vaccine must be willing to be hospitalized for between 5 and 7 days. They will come to the National Institutes of Health for follow-up visits weekly for the first month, after 8 weeks, in 6 months, and possibly 1 year. They must also avoid all vaccines (including seasonal flu vaccine) and allergy shots for 30 days before and after having the study vaccine.
• Participants will enter the hospital for the vaccine study visit. They will receive the vaccine as a nasal spray. Because the vaccine uses a live virus, participants may be contagious for the virus for up to 4 weeks. They will remain in the hospital in respiratory isolation for 7 days, or until they have two negative nasal washes taken 1 day apart. A negative nasal wash means that there is no live virus in the nose.
• After leaving the hospital, participants will keep a diary at home for at least 3 weeks. They will record their temperature, any symptoms, or other health changes every day during this time.
• Participants should avoid intimate contact with others for 28 days after having the vaccine. Intimate contact includes kissing on the mouth and sexual intercourse. Also, participants should not share kitchen utensils, drinking cups, towels, or hair combs with others. Intimate contacts will also keep track of any illnesses or symptoms they develop during this time.
• At the follow-up visits, participants will provide blood and swab samples for study.

Conditions

Healthy Volunteer

Keywords

Flu Vaccine; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of the Ad4-H5-Vtn recombinant vaccine in Ad4 seronegative humans when administered intranasally

  Ongoing

Secondary Outcomes (3)

• To evaluate the immunogenicity of the Ad4-H5-Vtn recombinant vaccine in Ad4 seronegative humans when administered intranasally

  Months 2, 6

• To determine the optimal dose for the nasal Ad4 vaccine platform, up to a maximum dose of 108 vp.

  Ongoing

• To monitor transmission to household and intimate contacts of vaccines and To monitor shedding and stability of recovered Ad4 recombinants.

  Ongoing

Study Arms (1)

Intranasal

OTHER

Ad4-H5-VTN intranasal vaccine administered in cohorts of 3 at increasing dosages

Biological: Ad4-H5-Vtn

Interventions

Ad4-H5-Vtn BIOLOGICAL

Intranasal

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All participant (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria:
• Age 18 to 49 years for vaccinees. Vaccinnees may be greater than 49 years of age at the time of booster vaccination. Age 18 to 65 years for household and intimate contacts.
• Able to provide proof of identity to the acceptance of the Principal Investigator or designee during enrollment.
• Available and willing to participate in follow-up visits and tests for the duration of the study.
• Willing to have samples stored for future research
• In good general health without clinically significant medical history.
• Negative b-HCG pregnancy test for females presumed to be of reproductive potential.
• A female must meet one of the following criteria:
• No reproductive potential because of menopause (one year without menses) or because of a hysterectomy, bilateral oophorectomy, or tubal ligation.
• Participant agrees to be heterosexually inactive or consistently practice contraception at least 21 days prior to enrollment and 28 days following vaccination. Acceptable methods of contraception include the following:
• condoms, male or female, with a spermicide
• diaphragm or cervical cap with spermicide
• contraceptive pills, Norplant, or Depo-Provera
• male partner has previously undergone a vasectomy for which there is documentation.
• intrauterine device

You may not qualify if:

• A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following:
• \. Any condition that, in the investigator s judgement, places the subject at undue risk by participating in the study.
• History of any prior disease or therapy which would affect immune or pulmonary function.
• Prior malignancy, except curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• History of radiation therapy or cytotoxic/cancer chemotherapy.
• History of diabetes mellitus.
• Immunodeficiency or autoimmune disease.
• Acute infection or a recent (within 6 months) history of chronic infection suggestive of immunodeficiency.
• Taking any medication which may affect immune function, except participants may be taking low doses of nonprescription strength NSAIDS (including e.g. ibuprofen or aspirin) or acetaminophen.
• Chronic respiratory disorders including asthma, emphysema, interstitial lung disease, pulmonary hypertension, recurrent pneumonia, or recent or ongoing respiratory tract infection. If a respiratory disorder is transient, defer immunization but do not exclude the participant.
• Active Hepatitis B or C infection (i.e. Hepatitis B or C positive serology with the presence of virus antigen or DNA. Ongoing viral replication will be confirmed by a Hepatitis B antigen or Hepatitis C viral load).
• Female of child-bearing potential who is breast-feeding or planning pregnancy during the 28 days following vaccination.
• Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to receipt of live virus vaccine, protocol adherence, or a participant s ability to give informed consent.
• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to
• enrollment.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Connors M, Collins PL, Firestone CY, Sotnikov AV, Waitze A, Davis AR, Hung PP, Chanock RM, Murphy BR. Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia--RSV recombinants or RSV. Vaccine. 1992;10(7):475-84. doi: 10.1016/0264-410x(92)90397-3.

  PMID: 1609551 BACKGROUND

• Couch RB, Cate TR, Fleet WF, Gerone PJ, Knight V. Aerosol-induced adenoviral illness resembling the naturally occurring illness in military recruits. Am Rev Respir Dis. 1966 Apr;93(4):529-35. doi: 10.1164/arrd.1966.93.4.529. No abstract available.

  PMID: 4286394 BACKGROUND

• Edmondson WP, Purcell RH, Gundelfinger BF, Love JW, Ludwig W, Chanock RM. Immunization by selective infection with type 4 adenovirus grown in human diploid tissue culture. II. specific protective effect against epidemic disease. JAMA. 1966 Feb 7;195(6):453-9. No abstract available.

  PMID: 4285433 BACKGROUND

• Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, Pullano AA, Kang BH, Ishida E, Zimmerman M, Kashyap N, Martins KM, Stadlbauer D, Pederson J, Patamawenu A, Wright N, Shofner T, Evans S, Liang CJ, Candia J, Biancotto A, Fantoni G, Poole A, Smith J, Alexander J, Gurwith M, Krammer F, Connors M. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021 Mar 1;131(5):e140794. doi: 10.1172/JCI140794.

  PMID: 33529172 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Mark Connors, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: March 7, 2013
• Study Start: March 6, 2013
• Primary Completion: January 9, 2018
• Study Completion: April 22, 2019
• Last Updated: October 7, 2019

Record last verified: 2019-04-22

Locations

US (1)